Bacterial and Parasitic Infections
With the constant evolution of pathogens and the growing threat of antimicrobial resistance, fundamental research plays a critical role in understanding the complex biology of bacterial and parasitic infections, such as Buruli ulcer, malaria, Golden staph, strep A, bacterial pneumonia and tuberculosis.
At the Doherty Institute, research employs a collaborative and multifaceted approach; from studying the intricate biology of bacteria and parasites and developing cutting-edge genomic surveillance techniques, to delving into host-pathogen interactions and developing innovative clinical trials and antimicrobial strategies.
Read more about our work on bacterial and parasitic infections.
2023 HIGHLIGHTS
Inflammation offers a crucial time in the fight against malaria
Once transmitted through mosquito bites, malaria parasites, such as Plasmodium falciparum, infiltrate the bloodstream, taking over red blood cells to rapidly multiply. The faster the parasite population grows, the higher the risk of severe disease, so time is of the essence. Research by the Doherty Institute and the Kirby Institute published in mBio, found that when the body experiences inflammation, the blood composition changes, hindering parasite growth. Led by the University of Melbourne’s Associate Professor Ashraful Haque, a Laboratory Head at the Doherty Institute, and one of the senior authors of the paper, the scientists found that this change could slow down the malaria parasites’ reproduction time by up to 70 per cent, offering a crucial window of time for live-saving medical interventions. This finding not only expands our understanding of malaria but also offers insights into potential strategies to prevent severe infection.
Elevated virulence explained by genetic mutation in new Strep A variant
The resurgence of scarlet fever and severe infections caused by the highly virulent, recently emerged M1UK strain of Streptococcus pyogenes, commonly referred to as Strep A, poses a significant health threat globally. In a study, published in Nature Communications and co-led by the University of Melbourne’s Dr Mark Davies, a Laboratory Head at the Doherty Institute, researchers were the first to detect the previously unnoticed spread of the M1UK strain of the bacteria in Australia. The team also made a significant breakthrough by discovering that the strain’s increased virulence stems from a genetic mutation in the bacteria driving the over-expression of a toxin that weakens the immune system.
International research initiative to advance genomic surveillance of Shigella flexneri
Flagged by the World Health Organization (WHO) as a priority pathogen, Shigella flexneri poses a significant threat worldwide due to its high infection burden, especially in low to middle-income countries, and its increasing resistance to antibiotics. In 2023, the University of Melbourne’s Dr Danielle Ingle, NHMRC Emerging Leadership Fellow at the Doherty Institute, established a global network of Shigella experts to improve genomic surveillance and better understand the bacterium’s evolution and epidemiology. They are developing a novel genomic classification method for the highly accurate detection of S. flexneri. The team plans to implement their findings in public health labs and freely distribute the tools to help officials detect and respond to outbreaks more effectively.
Advanced surveillance system can predict Buruli ulcer hotspots in Victoria
Once considered a rare infection, Buruli ulcer has become a major concern in the state of Victoria, one of the most highly endemic areas globally. Collaborative research, led by the University of Melbourne’s Professor Tim Stinear, Director of the WHO Collaborating Centre for Mycobacterium ulcerans at the Doherty Institute, has confirmed the critical role of native possums in transmitting M. ulcerans, the bacteria causing Buruli ulcer. By analysing possum excreta and epidemiological data, researchers found a strong spatial correlation between M. ulcerans-positive possum excreta and human cases. This led to the development of an early warning system using a computer model capable of predicting areas and times of increased risk of Buruli ulcer transmission. This sophisticated surveillance tool has the potential to reduce Buruli ulcer cases by alerting the public and healthcare providers to increased infection risks in specific areas, facilitating targeted public health interventions and contributing to the control of the disease in southeast Australia.
New tool charts bacterial genetic evolution, a step toward more effective antibiotics
Horizontal gene transfer (HGT), where bacteria share genes with each other, is a fundamental part of bacterial evolution. However, this exchange of genetic information can give bacteria new abilities, such as antibiotic resistance or increased virulence, which can lead to serious health implications. Researchers, led by the University of Melbourne’s Dr Gerry Tonkin-Hill, Group Leader at the Doherty Institute and the Peter MacCallum Cancer Centre, have developed Panstripe, a cutting-edge tool capable of estimating the speed at which bacteria can gain and lose genes. Using advanced statistical techniques, Panstripe dramatically surpasses the accuracy of existing methods, enhancing our understanding of how quickly bacteria can evolve to become resistant to antibiotics. These estimates are crucial for designing public health policies to prevent the emergence and spread of antibiotic resistance.
Pathogen genomics: advances and collaboration at AusPathoGen
At the second annual symposium of the Australian Pathogen Genomics Program (AusPathoGen), over 100 participants from Australia and New Zealand convened to discuss significant advances in tackling bacterial and parasitic infections. The event showcased key findings on Salmonella, Shigella and Mycobacterium tuberculosis, revealing cross-jurisdictional transmission clusters and multi-drug resistant strains. The symposium emphasised the critical role of pathogen genomics in national health strategies and the enhancement of real-time genomic data-sharing systems like AusTrakka. The event provided a great opportunity to foster collaboration and share insights with our partners in pathogen genomics across the two countries.
Innovative therapeutic strategy to disarm pneumonia-causing, antibiotic-resistant bacteria
The University of Melbourne’s Professor Christopher McDevitt, Head of Research in the Department of Microbiology and Immunology and co-lead of the Bacterial and Parasitic Infections Theme at the Doherty Institute, is leading groundbreaking research to combat antibiotic-resistant community-acquired bacterial pneumonia (CABP).
With a substantial $2.68 million grant from CARB-X, a global non-profit partnership led by Boston University aiming to accelerate antibacterial research to address the rising threat of drug-resistant bacteria, the project aims to develop an innovative solution targeting antibiotic-resistant bacteria commonly associated with CABP. The team has discovered a method to overcome the bacteria’s antibiotic resistance, thereby reinstating the ability of common antibiotics to effectively eliminate those bacteria and tackle CABP.
This project is only the second one in Australia to receive support from CARB-X, a testament to their innovative approach to addressing the global issue of antimicrobial resistance.
Multidisciplinary study elucidates the mystery of potent antifungal’s synthesis
Researchers, led by the University of Melbourne’s Dr Sacha Pidot, a molecular microbiologist and Laboratory Head at the Doherty Institute, have discovered that Nocardia, a bacterial species known for causing infections in humans, produce a powerful antifungal molecule called terpenomycin. Combining chemistry, genetics and molecular microbiology, the team uncovered the complex pathways leading to the production of terpenomycin. The findings reveal previously unknown and unusual mechanisms behind the production of this potential antifungal. This breakthrough underscores the potential of Nocardia species to be sources of valuable medicinal compounds. It also highlights the significance of exploring microbial diversity for advancements in medicine, offering promising prospects against fungal infections.
PUBLICATIONS
Here is a selection of papers published by our teams in academic journals on bacterial and parasitic infections:
Ganley M, et al. mRNA vaccine against malaria tailored for liver-resident memory T cells. Nature Immunology (2023). https://doi.org/10.1038/s41590-023-01562-6
Lacey J, et al. Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analysis. The Lancet Microbe (2023). https://doi.org/10.1016/S2666-5247(23)00068-X
Giulieri S, et al. A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteremia. Cell Reports (2023). https://doi.org/10.1016/j.celrep.2023.113069
Gonzalez de Vega R, et al. Spatial distribution of trace metals and associated transport proteins during bacterial infection. Analytical and Bioanalytical Chemistry (2023). https://doi.org/10.1007/s00216-023-05068-w
Loterio R, et al. Coxiella co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress-induced cell death. Proceedings of the National Academy of Sciences (2023). https://doi.org/10.1073/pnas.2308752120
